This project consists of two main areas of investigation. The first deals with the effects of opiates and opioid peptides on cellular proliferation in the mammalian brain. The research is directed toward an understanding of the basic mechanisms responsible for increased proliferation of glial cells originating from the subependymal zone of the rat brain following acute but not chronic systemic injections of morphine sulfate. The second phase of the research project examines the acute and chronic effects of morphine and other opiates as well as opioid peptides on the neurophysiological activity of hippocampal pyramidal cells recorded in vitro. Specifically, research is directed toward an understanding of the basis of morphine's excitatory action on these cells following application to slices of hippocampal brain tissue maintained in vitro. The project utilizes these techniques to examine questions concerning physiological mechanisms of reaction to acute exposure and development of tolerance to opioid agents which would not be possible utilizing in vivo preparations.